Progressive MS webinar transcript

Full text of our 2014 webinar with experts on progressive MS

Last updated: 22nd April 2016

27th November 2014

Ceri Angood: Hello, I’m Ceri Angood, MS International Federation’s Director of Programmes and I’m pleased to welcome you, wherever you are in the world, to our live webinar on progressive MS. Happy thanksgiving to those of you celebrating today!This is your chance to ask questions about progressive MS directly to international experts. We received a lot of questions in advance – thank you! Peer Baneke, our Chief Executive has just arrived back from Russia and has popped in to say hello.

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Peer Baneke: Thank you very much. Thank you all for the many suggestions you sent us for questions to answer. We’ve had questions about diet, about alternative medicine, about myelin repair and myelin protection, exercise and rehabilitation, about stem cells of course, and also about the search for a cure. Now, these are too many questions to tackle in one hour, in one webinar, so we’ll start off with progressive MS because that was the issue where most of you asked questions about.Ceri: Thank you Peer. Now, over to your host for the webinar, Dr Dhia Chandraratna.

Dr Dhia Chandraratna: Thank you Ceri. Hi, I’m Dr Dhia Chandraratna, Head of Research at the MS International Federation and I will be your host today. We are delighted to have with us two world renowned experts in MS, Professor Alan Thompson and Professor Olga Ciccarelli.Prof. Alan Thompson is the Chair of the International Medical and Scientific Board of MSIF and the Dean of the Faculty of Brain Sciences at University College London. Prof. Olga Ciccarelli is a Professor of Neurology at University College London and also one of our first ever Du Pre Grant recipients.Today they will be answering your questions on progressive MS. So let’s get started! Alan, as an introduction to the topic, can you tell us what is progressive MS?

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Prof. Alan Thompson: Let me begin my saying a few words about multiple sclerosis itself and then moving along to the progressive form. As many of you will know, MS is a condition which affects the brain, causes inflammation, damage to the myelin sheath, and damage to the nerve fibres themselves. It often affects young adults and it usually causes attacks or relapses that come and go over time. But then you also have the progressive form of MS and that basically is describing a gradual change over time, a gradual worsening of disability over time.There are two forms of progressive MS – primary progressive that occurs from the onset, right from the beginning people notice that they have some deterioration, usually in their walking which gets gradually and sometimes quite subtlety worse over time, and then there’s secondary progressive MS which occurs maybe five, ten or fifteen years after relapsing-remitting MS and again you notice this very gradual progression over time.Primary and secondary progressive MS probably constitute together up to 50-60 % of the MS population worldwide.Dhia: Thank you Alan for a very clear introduction. We have some questions coming in now – from Karen in Canada and Joanne in the United States. The first is a question to Olga. They want to know why there are no treatments for progressive MS. What are the challenges in finding treatments for progressive MS?

Prof. Olga Ciccarelli: That’s correct. We don’t have available treatments to slow down progression in progressive MS and this is due to the fact that we don’t fully understand the mechanisms of progression. So there’s been a lot of research and there has been progress on understanding these mechanisms but until we understand fully why there is a neurodegeneration causing progression it is difficult to treat it.Also there is the challenge in identifying outcome measures to use in trials to measure the efficacy of treatment in performing large clinical trials with suitable medications. There are a lot of challenges but this has been tackled in recent years and hopefully we will have some good news soon. Dhia: Thank you Olga. The next question is from Jan Zantingh in Lebanon and Linda Doubleday in New Zealand. They would like to know – this is a question to Alan – why isn’t more research being done on progressive MS? Alan: I begin by saying I agree completely with Olga that this is a more complicated form of multiple sclerosis and one which we don’t understand as well as the relapsing-remitting form. But actually there is quite a lot of research going on in the world. I think the last estimate, when we looked worldwide at all the research that is being supported, was up to $90 million spent on research into progressive MS.But there are a couple of points to make about this. I think it’s not very joined up so there’s research going on in different parts of the world independently and of course the key thing is that none of this research has got over the bar and resulted in a treatment. Until we have a treatment people feel there’s not a lot going on. There is a lot going on but there is a real potential to bring all this research together, to focus it more and to be more strategic in how we approach it. And that’s really why the Progressive MS Alliance was established.

Dhia: Thank you. And just following on from that we have a question from Kevin Kelly in Ireland and Kate Cherry from Australia. They would like to know what is the Progressive MS Alliance and what are they trying to achieve.

Alan: I have given an introduction to this already. The whole idea of the Progressive MS Alliance is to bring all of the research across the world together to try to tackle this very difficult issue. When you’ve got something that’s very challenging you need collaboration to try to understand it and then to treat it. The Alliance is about bringing together as many people as possible with expertise in the area to tackle the problems or the issues that are blocking or slowing treatments for progressive MS.

Olga mentioned some of those and they are around having good models of the disease, understanding what is happening inside the tissue of people with progressive MS, identifying targets for treatment, having trials both early and then larger more definitive trials, having outcome measures that we could use in those trials and then the hugely important area of symptomatic treatment and rehabilitation. So the Alliance is trying to drive this area forward.

It is an alliance of MS societies around the world brought together by the MS International Federation and its focus is upon treatment for progressive MS.

Dhia: Thank you. And just following on from that a question for Olga from Non Smit in South Africa and Sue Morris from the UK. Alan just talked about some of the areas that the Alliance is trying to focus on. Can you tell us what are the most promising areas of research in progressive MS?

Olga: The most promising is trying to define a treatment that slows down progression in MS and I think this can be done by researching the mechanisms of the disease. This is achievable by studying people with MS with a clinical assessment or an imaging assessment and trying to understand what is contributing to clinical progression.

Then an important area of research is evaluating outcomes which we can use in clinical trials to identify whether people are having a good response to the treatment to understand whether the treatment is effective for MS or not. And then there is important research trying to identify and measure for prognosis, so we want to know and be able to tell a person with MS whether it is likely to progress faster in a shorter period of time or perhaps slower is a long period of time. We want to give answers to individuals about their future, about what’s going to happen in the following years – something that makes a difference for individuals.

And then obviously there is the area of treatment trials, trying to bring together difference centres, different expertise worldwide, to perform these very challenging clinical trials to test the efficacy of the medication.

Dhia: Thank you Olga.

We know there has also been a lot of interest in other research areas and if we can raise the funds we would love to put on other webinars in the future. So, if you can make a gift, please use the simple form at the bottom of the page.

Let’s go back to our questions. The next question is to Alan from Dan Favotto from Australia and Karim Daya from Canada, and they would like to know, what are the best available treatments currently for progressive MS?

Alan: well, I make two points to begin with. The first is that we don’t have a specific treatment for progressive MS as Olga has mentioned earlier. But the second is that all forms of MS need a very active management plan. That is the same for relapsing remitting as it is for progressive MS. So health is really important, keeping yourself well is very important. Looking after yourself, a good diet, exercise, also very important. In progressive MS, you get a number of symptoms; difficulty with mobility, with bladder, with tremor, and all of these need to be treated symptomatically, and that’s crucially important. Of course rehabilitation is also key. It brings together all the symptomatic management, but also improves quality of life for people with progressive MS. So having progressive MS isn’t about not having active management. That is absolutely critical. In fact arguably, it is more important to be actively managing your condition when you have progressive MS, than with relapsing remitting MS.

Dhia: Thank you. The next question is to Olga and it’s from Bergthora Bergsdottir from Iceland and Gillian Hirsch from Israel, and their question is: ‘are there new treatments on the horizon for progressive MS?’

Olga: Yes, definitely there are new treatments undergoing clinical trials, so they are already being tested in phase II or phase III clinical trials. Others are more experimental, so perhaps further away from clinical trials. These are treatments that are trying to target neuroprotection, so trying to protect the tissue from further damage, and then you must have heard of treatments that are trying to repair what has been damaged. I think these are the two main streams, either protect the central nervous system, the cells from further neurodegeneration or trying to improve the conduction along the nerves, trying to restore some of the function, so repair what has been lost.

There are medications, completely new medications being discovered, but also some older medications that are now going to be tested in progressive MS to see whether they can have an effect. So I think as Alan said there is a lot going on, and we expect, we hope, to have something available in the near future.

Dhia: Great! The next question is on stem cells for Alan and it is from Vladislava Vassitskina from Estonia and Christian Oleson from Denmark and Teresa de Marcos from Spain. And they would all like to know: is there hope for stem cells as a treatment for progressive MS?

Alan: So again, I will begin by saying that stem cells are a topic that has been discussed now over a number of years, and it’s one that there’s always been great hope for, but it’s taking quite a long time to realise that hope. So where are we at the moment?

I think we’ve had a number of small studies looking at different forms of stem cells. There are many different kinds, and insofar as those small studies can be evaluated, they do show some encouraging evidence, but none of them are absolutely clear in their outcome. And what we need with stem cells is larger trials, or bringing together the small trials to get a definitive answer. So this perhaps is rather a long winded way of saying that yes there is potential and there is hope.

Stem cells suppress inflammation, but they also encourage repair or remyelination. So you’ve got two actions that could be very useful in multiple sclerosis. So there is hope, it is a difficult area to do definitive studies, but they are ongoing at the moment and they are developing very well. So I think it’s a question of watching this space. But we need proper trials and we need to make sure that if people want to get involved with stem cells they do so through proper trials and not in any other way.

Dhia: The next question is to Olga and it’s from Jeyachitra Alagar from India and Rebecca Anderson from the USA and Judy Slater from the UK. The question is: what is the role of rehabilitation and exercise in managing progressive MS?

Olga: As Alan mentioned before, rehabilitation is essential in the management of progressive MS and has to focus on the person with progressive MS. So it is not something that can be advised to [EDIT: a wide audience], it has to be for a very specific case.

It is important to improve mobility of the person, to improve exercise tolerance, help to maintain cognitive function, help to keep people in employment or help people to come back to employment if they want to. It is important to manage the person with MS in general to improve the quality of life, to reduce impact of symptoms, so we include obviously symptomatic treatments.

But exercise – everyone should do it, I know I should, Alan probably and everyone here should do exercise! So I always say this is not something exclusively for progressive MS, it is good to have it as part of a daily routine for everyone, but in particular for people with progressive MS it is essential to keep mobility, to keep a general wellbeing to improve quality of life.

Dhia: Thank you Olga. We have a question now from Drew Heap and Debra Tiegren in the USA, Brian Lee from Australia and also Monica Silva from Canada. And their question to Alan is: ‘is there any research on myelin repair and neuroprotection? What are the advances in that area?

Alan: Well the straightforward answer to that question is yes. There is a lot of research in myelin repair and in neuroprotection. When you’re dealing with progression, which of course is about loss of axons, loss of tissue, then protecting the brain or repairing the brain are two really critical areas to try and develop. But they are complex and challenging.

We talked a bit about stem cells earlier, which of course is one of the approaches to myelin repair and there has been some progress in that area. And Olga mentioned neuroprotection which is not something we want to do just for progressive MS but for a whole range of neurological conditions, there’s also been quite a lot of activity. There is a lot going on here in the UK, some going on in the States and in other countries globally. There are studies now in progress which are looking at a number of drugs which we are using for other conditions but which actually have a neuroprotective component to them, and they are happening now; the MS SMART trial in the UK, SPRINT MS in the States.

We are focusing on this area and as I say, it is challenging. But through the Progressive MS Alliance we would be hoping to have far more studies in this area, and in a finite period of time, to have treatments.

Dhia: Great. We have a question now from John Davis sent to us by email, and the question is how do we know if drugs are having an effect on progressive MS, we don’t know how our progression would have progressed without the drug, so how do you measure efficacy? Who’s going to take that?

Olga: This is a very good question. We always get this question. So how do I know whether a drug is effective for me or not, since I don’t have myself without the medication? But if a medication is licensed and is available for prescription, it’s a medication that has been tested in clinical trials against a placebo, which is a tablet without a chemical effect. So we assume that it is an effective medication.

Whether it is helping that specific person then is really down to discussion with the individual whether he or she has noticed any change over time. Has she noticed that the course of the disease? Whether progression has stabilised or maybe has improved with the medication? So it’s really coming from discussion and communication with their own doctor.

Alan: I will just add to that, that it is very difficult as an individual to know whether a medication is having an effect so that is why clinical trials are so critical. You can’t tell from an individual experience. In clinical trials we’re not just looking at what’s happening to the person with MS, we’re also looking at things like their MRI scans and there we can see the rate of tissue loss and if that is actually being slowed.

I think that with a person with MS you can get a sense over a period of time, perhaps 6 or 12 months or even longer, whether that gradual change has now plateaued or maybe even improved. I think it is difficult but not impossible to detect that kind of change.

Dhia: Thank you, we have a question coming in now from Twitter from David Seffer, who asks, “Interferons have completely stopped my relapses. Should I continue to take them when I have evolved progressive MS?”

Alan: It’s a good question and one which comes up in clinic a lot. We know that the main effect of interferons is to reduce relapses and if it’s working well then you’re not having relapses. There’s a difficult question as to whether you’re no longer having relapses but you think you may be getting very subtly and very gradually worse; and is that progressive MS? And should you stop your medication? And if you do stop your medication are you likely to have attacks?

It’s not a very straightforward question. MS Is a very individual condition and I think it’s very important that every patient discusses their condition with their own neurologist to decide what is best for them. Sometimes it can be quite difficult. We sometimes have this tendency to stop taking medication when it’s being effective, so that’s something we should avoid doing.

Dhia: The next question is also coming from Twitter, “Does MS progress faster in men than in women?”

Olga: That’s a good question. There is some evidence that men with secondary progressive MS progress faster than women with secondary progressive MS. There is also possibly more cognitive impairment than women. In primary progressive MS the difference between the two genders is less clear. I think that in general the differences are more at the individual level than an effect of gender but it is definitely worth discussing.

Dhia: This next question has been asked by many people on email and twitter, asking how they can get on clinical trials?

Alan: There are a number of different ways. Firstly, they will be attending their own hospital and their own neurologist and I anticipate the MS team there will know about what trials are going on. They can discuss them with the person with MS and discuss what the inclusion criteria are.

Of course you can go on the web and you can look at websites. MS International Federation has a very good website. There are also the MS societies and many will flag up the trials that are going on. Some trials have their own websites so you can see what’s happening directly. It can be a little confusing and I think that the first step should always be your local MS team.

Dhia: The next question from Twitter is from David Seffer, “Is there a way to definitely tell when one has passed from relapsing remitting MS to progressive MS?”

Olga: There is no way to tell you now definitely have progressive MS, it is something which happens more retrospectively. During clinical assessment we tend to discuss how MS is evolving. When a person reports progression of symptoms in the absence of clear episodes of relapses, so there is evidence that neurological evidence is accumulating despite the fact there are no acute episodes, then this may have become progressive MS.

But what happens is that after a certain period of time you come back and you say, ‘well this has been now two years or three years that I’ve been progressing without acute relapses’. There is the difficulty that it cannot be [assessed] over one day or one month, it is something which is identified over a longer period of time. It comes out through discussion with your doctor because we do not have a single test which says, ‘you now have progressive MS’.

Dhia: The next email has come in from Loretta, who talks about the similarities between Alzheimer’s and multiple sclerosis. She wonders whether it is worth studying the similarities between the two conditions?

Alan: This is a very important question because we often look at these conditions in isolation and there is a lot to be learnt by looking across neurological disorders. I think particularly for progressive MS where we know there is tissue damage, tissue loss and neurodegeneration that makes it more similar to certain other conditions like Alzheimer’s or motor neurone disease.

It’s looking at the basic mechanisms which underpin or underlie that neurodegeneration that is important. So that is why it is important to look across these different conditions and the literature, because these conditions are very challenging. Nobody understands all aspects of any neurodegenerative condition. If we can get some clues from one which we can then apply to another then that is very useful. So a very good question, particularly for progressive MS.

Dhia: This one has just come in by email and it asks, is the Progressive MS Alliance focusing on the immune and autoimmune factors?

Alan: The Alliance is focusing on all mechanisms that could result in progression so the immune system plays a big part. Both parts of the immune system. The innate immune system is perhaps less studied so is becoming more of a focus for research.

The immune system is being studied and particularly the relationship of the immune system to demyelination and neurodegeneration and how all of these things link up. If you impact on one what effect will that have on the others? So those relationships are key and the immune system is absolutely central to that. A very good question.

Dhia: Another question has come in via email, from Anne. She would like to know more about nutritional approaches and any particular diets and if there is any benefit on progressive MS?

Olga: We do not have any evidence that a specific diet helps to slow down or stop progression in progressive MS. I get this question all the time in clinic, ‘should I go on this diet or that diet…’. My personal advice is that people are free to try whatever diet they like as long as people don’t expect to see huge improvements from that specific diet. I know that online you can see reports from people who have shown incredible improvements from diets.

I think that some of the diets are also quite challenging. If it is a very strict diet it’s difficult to follow; it is also sometimes quite difficult for the whole family because you have four or five different meals with different preparation, then it becomes an obsession, then you feel guilty when you don’t follow the diet.

So in general it’s a bit like exercise, everyone should follow a healthy lifestyle doing exercise and eating a healthy diet. But we cannot recommend any specific diet because we do not have the evidence to do so.

Dhia: We have a question from Kholoud in Saudi Arabia, asking if there is a role for Alemtuzumab in treating progressive MS?

Alan: The main evidence at the moment is that Alemtuzumab has a very strong effect on relapses and often results in no attacks. Patients often find that they are improving both in terms of not having attacks but in terms of their mobility so they see changes. A specific effect on progressive MS has not been demonstrated and that’s much more difficult.

Whether or not – and this is another quite challenging question – whether or not suppressing relapses and inflammation in the earlier part of MS has an impact on the progression that might follow is a very difficult question which has not yet been answered. The relationship, if you like, between that early inflammatory phase and the progressive phase.

When we look at scans of people with MS and we look right from the beginning, what we see is that although they have a lot of lesions on their scans when they have relapses they also have a gradual loss of tissue right from the very beginning of their MS. So there is a very subtle neurodegenerative part right from the beginning. It may well be that that continues and may not necessarily be affected by suppressing the inflammation.

It’s difficult to say and again it’s back to this relationship between inflammation and neurodegeneration. Does one cause the other, or is one a reaction to the other? That is still a very fundamental question which we are yet to get a very clear answer on.

Dhia: There’s another question actually, related to that, coming from twitter and this is about brain atrophy and it’s about MS and the relationship with brain atrophy in the longer term and they’ve also asked if you can explain brain atrophy for a lay audience.

Olga: Ok so it’s a good question. Brain atrophy you can see over time as reduced volume of the brain. So everyone, over time, develops some volume loss everyone sitting here, we’re all losing some neurons.

Alan: Some more than others!

Olga: Yes, some more than others!

But it has been recognised that the people with MS have a faster loss of brain volume over time. But as you know as part of aging there is also some development of brain atrophy. The surviving tissue adapts to the loss of volume and it creates connections to continue functioning in a sufficiently acceptable way. So although there is brain atrophy there is also some plasticity of the brain for which neurological functions are maintained, cognitive functions are maintained.

What happens in progressive MS is that the development of brain atrophy becomes more significant. This is why it is used as an outcome measure in clinical trials. What we want to see is a treatment that slows down or has an effect on reducing the development of volume loss.

Alan: So it’s actual loss of tissue over time and it’s more loss of tissue than you would see with normal aging which is what we’re all doing!

Dhia: We’ve got another question coming from twitter from Nick who wants to know: How critical is basic physiological research to finding a cure and how does this translate to the clinic?

Alan: That’s quite a challenging question.

Dhia: Yes.

Alan: I think that basic physiological research is really important because we do know that in MS normal physiological processes are affected. There is involvement of what we call the autonomic nervous system which has an effect on these physiological mechanisms.

We also know – and this is back to the exercise literature – that over time people tend to do less and as a result they do even less so you become deconditioned. So actually physiological wellbeing, particularly around cardiovascular respiratory, is really important. Whether that tells us more about the underlying mechanisms about MS I’m not so sure. I think it’s very important for the person with MS and very important to manage and understand but perhaps not fundamental to the actual finding of a treatment for progressive MS.

Dhia: We’ve got another question from Sally Beck via twitter. There’s sort of two questions but she’s linked them. What are your thoughts on CCSVI and any recent trials using statins? They both increase the blood flow.

Olga: I think it’s fair to say that we have no evidence of any effect by CCSVI on the brain or on progression in MS. I’m aware of people who have had CCSVI either as part of clinical trials – especially in the States – or as private treatment and I come from a country where CCSVI has been used a lot and still currently used but it is not something we can recommend because there is no evidence that it is effective.

Alan: Well I think in relation to CCSVI I think that when the initial positive reports came out in the literature there was a lot of excitement about it. There was a huge response from people with MS to look at this exciting area and as a result the MS societies funded a lot of research to look at the underlying mechanism of CCSVI, which is really about dilating veins. [There were] also much more detailed studies of the effect on people with MS and that was a useful exercise because we now have a very large database.

[This] research base really shows little or no effect on underlying mechanisms and little or no treatment effect but it is based on really sound evidence. That’s all we have to approach any of these potential new treatments because you can never be sure until you have done that really hard research approach.

Olga: I wanted to add that I know people who had CCSVI treatment and they felt better and I always get this question in clinic. ‘Well you say the clinical trials show no evidence of this treatment but in fact I had it and I feel better and I had it and I feel the same or I had it and I feel worse.’

You come back to the question we had earlier on, how do I know that the treatment is effective for myself? We are talking about treatments being tested in large clinical trials. Very sound research but then obviously an individual person may feel that it has an effect but on a chemical level and on a clinical trials level that effect hasn’t been observed. If that makes clear?

Alan: Yes

Dhia: Yes.

Alan: So can I now go on and talk about the statins? I think statins are really very interesting. I mean they are obviously an incredibly useful group of drugs which help many people with a whole range of different conditions. They have been looked at in relapsing remitting multiple sclerosis and there have been several trials and they’ve been mainly negative but there has been recently a trial in progressive MS which was published in The Lancet which demonstrated an effect both on the measure of brain atrophy but also on the patient’s own level of mobility or disability.

That’s the statin trial which looked at 80 milligrams of simvastatin, [which] has been positive. It was a relatively small phase 2 trial so we now really need to go on to do a major phase 3 trial. So that’s an ideal study to be done internationally involving many of the MS societies and also perhaps the Progressive MS Alliance. I think statins are very interesting and it’s interesting that they seem to work in progressive MS but not in relapsing remitting MS which gives you some indication of what the mechanism might be.

Dhia: There’s a question from Dorothy in California. In order to cure MS do you have to destroy and rebuild the immune system?

Olga: Quite challenging. I don’t think so. I don’t think you have to destroy and rebuild the immune system, no. The approach so far has been to try to modulate it. Try to improve the response in a way that is the correct immune response but destroying and rebuilding may be a bit extreme. I don’t think that’s the approach we are doing so far, no.

Alan: We can remember that in MS we have an altered immune system, most of it functions very well, in fact some of it might over function, so actually it’s much more as Olga said, we use the word ‘modulate’ to try and influence the immune system so that it functions more normally. That’s not about rebuilding.

Dhia: Thank you. Alessandro in Italy wants to know more about any functional MRI studies in relation to progressive MS and also in particular in relation to spinal cord studies.

Olga: Alessandro, it’s a very good question. As you know, scanning the spinal cord with MRI is very challenging, for several reasons. It’s a very small structure so it’s very difficult to image. But definitely there’s been study with functional MRI and there will be more studies in the future.

The question is to try to overcome the challenges and design a study which can give some important understanding of the mechanism of the disease. But definitely there are functional MRI studies of the spinal cord in MS and more I think are due to come.

Alan: I think it’s probably also important to make the point that when we say ‘functional MRI’ what we’re talking about is using imaging to actually, as it says, see how the brain functions when it is doing tasks so you have an idea of the working brain.

It’s not just taking static pictures of the brain. You’re looking at what the brain is actually doing as we are doing things or thinking or acting so it gives you a real insight into how the brain is changing over time and therefore how the effect multiple sclerosis can have on the brain itself.

It’s also very useful in looking at things like rehabilitation to see how you might be able to address some of the problems with brain function and improve it so it’s a very powerful tool. It’s quite a complex tool but one with lots of potential for the future.

Dhia: Thank you. We’ve just received a question form Paul via twitter. He says ‘After sexual intercourse I find my symptoms clear for a short while, is there a medical reason why?’

Olga: I can’t think of any medical reason why this is happening and no, I don’t think we have an answer for this.

Dhia: OK. Rachel, via email, just wants to know a little more about the clinical trials process. For example what does phase 1, phase 2, phase 3 mean?

Alan: So that’s a really very good question and I think it prompts us to just to talk a little bit about how you get from identifying a potential treatment to licensing a drug and this is a long journey if it’s a new drug which can take anything up to ten or twelve years.

If you think that you’ve found something in the laboratory which might actually have an effect in the central nervous system, which will in turn have a useful effect in MS, the first thing you have to do is to do some further studies involving animals to actually see if there is any danger to this agent.

The next is then doing small safety study in small groups of people that don’t have any condition, that don’t have MS and then you move on to studies that will involve people with MS. Again small studies which will be looking at side effects and at safety. And that would be first-in-man trials or phase 1 studies.

You then go on to do phase 2 study which is larger and is actually looking at efficacy. Is this drug useful? But it may not be looking at a clinical measure, it may be using imaging or some protein in the blood or in the spinal fluid to see if there’s a really clear beneficial effect from this agent.

If that’s true you’ll then move on to what we call a phase 3 trial which is the large, definitive, clinical study which will be the kind of study to move on to the drug being licenced and used as a treatment in the population.

Quite a lengthy process. Now, if you have drugs ‘off the shelf’ that are already being used for another conditions, and this has certainly been the case for some of the drugs we have been looking at in progressive MS, then of course you can move quite quickly to a phase 2 or phase 3 trial without any of the earlier work and that’s why repurposing of these agents is a very, a short cut to potential and new treatments for multiple sclerosis.

Dhia: Are there any promising agents around that have been looked at in repurposing trials.

Alan: Well there are. The statins which we talked about earlier are a really good example of a repurposing agent. So we know they lower cholesterol, we know they reduce risk factors and now we have a sense, an indication that they may be useful in progressive MS but now we need a phase three trial.

I think when we go back to neuroprotection a number of the drugs which we know to be neuroprotective are drugs which are used in epilepsy.

There are many I could mention and these are the drugs we are now looking at in MS. Phenytoin is an agent which has been around for many years in epilepsy. We are looking at this in optic neuritis to get a sense of whether or not it could have a neuroprotective effect. Lamotrigine is another and there’s a whole range of existing agents so repurposing is very important.

Dhia: Thank you, we have a question from Cindy in London by email and she wants to know if there is any effectiveness of oxygen treatments in progressive MS?

Olga: Yes, oxygen therapy has been studied and some people are using it. Some people report improvements in their energy level. I don’t think that the evidence of the effect in the mechanisms of progression is there already so this is not something that is recommended as a first line treatment for MS.

Alan: I think I probably emphasise the fact that there is not a sound evidence base to support what we call hyperbaric treatment in MS. It came about as a treatment when I was starting in MS nearly 30 years ago and there is not a sound evidence base so I would not be enthusiastic about exploring it.

Dhia: We have a question from Martin via Twitter. He asks “Is Fingolimod as dangerous as the sources I have read on the internet claim?”

Olga: Fingolimod, as with any other treatment we use – not just in neurology, in any medical speciality – has a list of side effects. So this is why every time it is prescribed for a person with MS we have to balance the benefits with the side effects. The person has to be informed about the possible risks but also see what it is useful to try this medication to improve for example the relapse rate.

It is true it is associated with side effects but I think that any medication has side effects. Even aspirin! I always say to my patients, if you ever read the list of aspirin you wouldn’t take that. Everything comes with benefits and side effects.

Alan: And I think that is an important point. All the time you are looking at the benefit and the risk. There is a risk benefit analysis. It tends to be the case that as the treatments become more effective they are stronger and they often have stronger side effects. Of course that is why we wouldn’t use very strong drugs with very strong side effects in somebody with very mild MS. You would certainly think about using it with someone who has very active MS, and this is the balance of the discussion you would have with someone all the time with the person with MS and make a decision with them.

Olga: And in case of aggressive treatment or treatment with the worst safety profile then you keep engaged with the medical team, the MS specialist and come back for regular follow up and blood test. There is follow up, you don’t only give them medication and then not see the person anymore. You continue to monitor the effect and possible side effects of the drug.

Dhia: We’ve got through a lot of questions and thank you for answering so many of them. But unfortunately we’re running out of time so I’m just going to ask one final question to Alan: If I was recently told I had progressive MS, what would the future look like for me?

Alan: I think if you were told you had progressive MS the first point is that you would look after yourself well. It doesn’t change anything. You look after yourself, you have to actively manage your condition as you would any other form of MS.

I think you would keep really abreast of research activity as that whole area has exploded and it’s incredibly exciting. I think particularly to link in with the activities of the Progressive MS Alliance. You may even consider becoming involved in a clinical trial, which would be an excellent thing to do. And you would anticipate a treatment for progressive MS in a finite period of time.

I think it is positive, very positive. And much more positive now than even five years ago.

Now I’d like to pass over to Olga who will talk about how MS International Federation has supported her in her career.

Olga: Yes so I’m very grateful to the MSIF because when I finished my training in neurology I was awarded a Du Pre grant from the MSIF, this was in 2000, not sure I had to disclose the year! So this allowed me to come to the UK to work with Alan and Professor Miller and learn more about MS.

At that time we did not have [many] treatments available for MS so a lot has changed really in 14 years. This is an excellent organisation that has provided funding for young researchers to move abroad and have experience of how things work in other countries, in this case UK. To develop a passion for MS, improve their research skills and clinical skills.

So yes, a big thank you to the MSIF. I think if you enjoy this webinar what we want to ask you is to make a donation to the MSIF, in order for this kind of activity to be repeated in the future.

Also send your feedback if you want to make changes for the future, this has to be interactive process. But we also need donation to give grants that allow young researchers to come to UK [and] but also other locations to improve understanding and discovering treatments for MS.

So I got the figure of about $40,000 dollars, that’s about €50,000 to support five young researchers to get out of their own countries, come to the UK [and other countries], learn more about MS, learn about symptomatic treatment, learn more about the challenging medications. Then go back to their own countries to share this knowledge with their teams. So this is why we need your help. Make a donation, whatever you like. Even $1 or €1 will be helpful to help the MSIF to help them fund more research into MS and with the purpose of today, into progressive MS.

Ceri: Thank you. It just remains for me to thank our wonderful world renowned experts, Professor Thompson and Professor Ciccarelli and our wonderful host Dhia for answering so many of your questions. Thank you for spending some time with us and sending in your questions. Good bye and see you next time.